Abstract
Simple SummaryThe pathophysiology of radiation pneumonitis (RP) after thoracic cancer radiation treatments is still not completely understood although the identification of underlying RP mechanisms may improve the therapeutic window of thoracic cancer patients. The aim of our retrospective study was to explore the dose–response patterns associated with RP by a multi-center voxel-based analysis. In a heterogeneously treated population of 382 thoracic cancer patients, we confirmed the previously described heart–lung interaction in the development of RP. The empowerment of VBA with a novel description of dose map spatial properties based on probabilistic independent component analysis (PICA) and connectograms provided valuable additional and independent information on the radiobiology of RP.This study investigates the dose–response patterns associated with radiation pneumonitis (RP) in patients treated for thoracic malignancies with different radiation modalities. To this end, voxel-based analysis (VBA) empowered by a novel strategy for the characterization of spatial properties of dose maps was applied. Data from 382 lung cancer and mediastinal lymphoma patients from three institutions treated with different radiation therapy (RT) techniques were analyzed. Each planning CT and biologically effective dose map (α/β = 3 Gy) was spatially normalized on a common anatomical reference. The VBA of local dose differences between patients with and without RP was performed and the clusters of voxels with dose differences that significantly correlated with RP at a p-level of 0.05 were generated accordingly. The robustness of VBA inference was evaluated by a novel characterization for spatial properties of dose maps based on probabilistic independent component analysis (PICA) and connectograms. This lays robust foundations to the obtained findings that the lower parts of the lungs and the heart play a prominent role in the development of RP. Connectograms showed that the dataset can support a radiobiological differentiation between the main heart and lung substructures.
Highlights
Radiation therapy (RT) represents a fundamental treatment strategy in thoracic oncology
A group of patients was treated for Hodgkin lymphoma (HL) at the University “Federico II” of Napoli (Comitato Etico per le Attività Biomediche, IRB 222-10) with 3D conformal RT (3D-CRT) [15,16]
A second group was treated for locally advanced non-small cell lung cancer (NSCLC) at the University of Texas MD Anderson Cancer Center of Houston (IRB 2008-0133) with image-guided intensity-modulated RT (IMRT), and a third one with passive-scattering proton therapy (PSPT) [17,18]
Summary
Radiation therapy (RT) represents a fundamental treatment strategy in thoracic oncology. The current clinical practice in treatment planning relies on safe parameters such as mean lung dose (MLD) and lung volume receiving at least a certain level of dose (e.g., V20 Gy) to estimate lung toxicity risk by assuming that the entire lung tissue shares the same radiobiological patterns [3]. Regional difference in lung radiosensitivity is an old story [4,5,6]. While a commonly accepted pathophysiological picture considers the lungs as parallel organs, the higher incidence of lung injury in the lower lobes, together with the differences in regional functionality revealed by nuclear imaging studies, indicates highly heterogeneous structural composition, functional capacity, and sensitivity to radiation. A greater risk of RP after irradiation of caudally located lung tumors has been acknowledged in [7]; the underlying local mechanisms still elude a thorough understanding
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